ida safitri laksono - seminar nasional, clinical · pdf filemyocarditis, psychosis,...
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Ida Safitri Laksono
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275639
201252
136088
255817
134065
2000 2001 2002 2003 2004
Number of Typhoid fever cases yearly
13
9.5
6.4
12
6.2
2000 2001 2002 2003 2004
Incidence rate per 10.000 people of Typhoid fever cases yearly
Subdit Surveillance EpdMinistry of Health
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Bulletin WHO 2008
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Host barriersLocal : pH, GIT motility , intestinal flora General : humoral and sellular immunity
OrganismNumber of microbesVirulence (serotype)
Antibiotic resistance
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Intestinal Epithel
Lamina propria
phagocytocis
Inflamation response
endotoxin (local, systemic)
Plaque PayeriMultiplication
Thoracic Duct
Primary bakteremia circulation
Target Organ RES (Liver, spleen, bone marrow)
Other organs (metastatic)
Secundary bakteremia
Local: inflamationSystemic: cytokine
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Day -15 Day 0 Day 7 Day 21
370C 400C
Incubation periodAsimptomatic
Invasive periodIntermittent feverHeadacheMalaiseAbdominal painConstipationDiarrhea
Typhoid phasePersistent feverBradicardiaHepatomegalySplenomegalyConstipationDiarrheaRose spot
ConvalescenceCarrierRelapse
Complication
Fever
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Not specific symptoms and signsFever ≥ 7 daysGastrointestinal symptomsVomiting, Diarrhea / obstipation, Meteorismus
Delirium, decreasing consciousnessAdolescent ~ adultToxic appearance, dehidrated, Typhoid tonguehepatomegaly, splenomegaly
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FeverChillingAbdominal painNauseaVomitingDiarrheaObstipationRavingUnconsciousnessTyphoid tongueEpigastric painHepatomegalySplenomegaly
10 25 50 75 100
Sri Rezeki H, Tumbelaka AR, Satari HI. Sari Pediatri 2001;4:182-7
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Laboratory scheme of typhoid fever
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Blood countsleucopenia, aneosinophilia, relative lymphocytosisthrombocytopenia
Increasing BSR, Increasing SGOT/SGPTSerological test : IgM & IgGCulture of Salmonella typhi
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Serological test : Widal test, Tubex – TF, etc
DNA probe
IgG of outer cells membrane
Immunoblotting (Typhi‐dot)
PCR (polymerase chain reaction)
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Bhutta ZA. Current concepts in the diagnosis and treatment of typhoid fever. BMJ 2006;333:78‐82.
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Widal test, since 1896O antibody, established earlier but for short time only (4 ‐ 6 months), H antibody, later and stay longer (9 months – 2 years), Vi antibody, late (persist in carriers)
Interpretation of Widal test should be taken carefully, depend on : Disease stadium Laboratory methodsEndemicity of diseaseImmunisation history
Nsutebu EF, Ndumbe PM, Koulla S. Trans R Soc Trop Med Hyg. 2002 Jan-Feb;96(1):64-7.
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Advantages of Widal test
Olopoenia LA, King, AL. Widal agglutination test - 100 years later: still plagued by controversy. Postgrad Med J 2000;76:80-84.
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GROUP SEROTYPE ANTIGEN O ANTIGEN HPHASE I PHASE II
A S. paratyphi A 1, 2, 12 a -B S. paratyphi B 1, 4, 5, 12 b 1,2
S. typhimurium 1, 4, 5, 12 i 1,2C S. paratyphi C 6, 7 c 1,5
S. Cholerasuis 6, 7 c 1,5D S. typhi 9, 12, Vi d -
S. enteritidis 1, 9, 12 g, m
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Out of 103 patients (clinical and cultural proven typhoid), TUBEX pos in 86.4%, Typhidot 74.7%, and Widal 69.9% In non typhoid group, Tubex pos in 25%, Typhidot 3.8% and Widal 26,9%Maximum number of Tubex and Typhidot were positive in patients with 7 –14 days of fever, while Widal was mostly positive in children with fever of more than 14 daysSensitivity, specificity, PPV and NPV for the tests
Tubex 86.4 84.6 95.7 61.1
Typhidot 74.7 96.1 98.7 49.0
Widal 69.9 73.0 91.1 38.0
Jaffery G, Hussain W, Saeed, Anwer M and Maqbool S. Annual Pathology Conference, 2003, Pakistan and 3rd Scientific Conference of Paediatric Association of SAARC Countries 2004, Lahore
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Tubex TF dibandingkan dengan Uji Widal pada pasien dengan biakan darah dan/atau PCR
RSCM, RS Persahabatan, RS Tangerang , Mei – Oktober 2006 Diperiksa 52 kasus, 27 laki2 dan 25 wanita dengan usia tertua 20 – 30 tahun (53.8 %)Semua pasien telah memenuhi Skor tifoid Nelwan > = 8 dan klinis memenuhi syarat demam tifoid.Tubex TF dibanding uji Widal terhadap skor itu menghasilkan
Sensitifitas 100% dan 53.1%Spesifitas 90% dan 65%Nilai prediksi positif 94.1% dan 70.8%, prediksi negatif 100% dan 46.4%Ratio likelihood (+) 10 dan 1.51, Ratio likelihood (‐) 0 dan 0.72AUC ROC Tubex 5.91 dan Widal 0.591, sangat berbeda bermakna
Surya H, Setiawan B, Shatri H, Sudoyo A dan Loho T. Diunduh dari http:/pacbiotekindo.co.id/tubextf.html, 29.11.2009
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Intra intestinal tract
▪ peritonitis, ▪ bleeding, ▪ perforation
Outside intestinal tract
▪ encephalitis▪ pneumonia▪meningitis▪ osteomyelitis▪ hepatitis
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One third of 102 cases develop complicationsAnicteric hepatitis, bone marrow supression, paralytic ileus, myocarditis, psychosis, cholesystitis, osteomyelitis, peritonitis, pneumonia, hemolysis, and SIADHIf hepatitis is excluded, the rate of complications is 11 %.
A child with splenomegaly or thrombocytopenia had 1.5times higher risk, where as a child with leucopenia has 2times risk to have complications.A child with both splenomegaly and thrombocytopenia or leukopenia had 2.5 times higher risk.
Alam Sher Malik. J of Trop Ped 2002;48:102-8.
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IrritabilityDecreasing consciousness (late stadium)Abdominal distensionAbdominal painDefanse musculaireLowering intestinal soundsDisappearance of hepatic dullness
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Clinically difficult to differentiateNeed supportive labsNasogastric and anal tube should be insertedAbdominal x‐ray (3 positions)Unequal air distributionAir fluid levelHepatic area radio lucent Free air at abdominal wall
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Supportive :Fluid therapy, dieteticElectrolyteAcid base
Causal :Medicamentous (antibiotics, steroid)Surgery (complication therapy)
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FluidMaintenance, D5 : NaCl 0.9% (3:1)Additional 12.5% for each 10 C increment
DieteticSolid foods could be given as soon as possible, instead of conventional strained foodLess fibers and stimulating foodNot to strict
Acid base correctionsElectrolyte corrections
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Bhutta ZA. Current concepts in the diagnosis and treatment of typhoid fever. BMJ 2006;333:78‐82.
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Antibiotics Sensitive Intermediate
Resistant
Ampicillin 34 10 54
Amoxycillin 28 6 66
Nalidixic acid 64 12 24
Chloramphenicol 46 40 24
Cefixime 80 14 6
Azithromycine 78 22 0
Cotrimoxazole 64 0 36
Ciprofloxacin 84 1 15
E Hartoyo, A Yunanto, L Budiarti. 3rd Congress of Pediatric Infectious Diseases. Cebu City, Philippines, March 2006
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Chloramphenicol100mg/kgBW/day oral, max 2 gram, 10 daysNot recommended for cases with leucocyte count <2000/Ul
Cotrimoxazole6mg/kgBW/day, 10 days
Amoxicillin 100 mg/kgBW/day, 10 days
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Ceftriaxone (cephalosporin 3rd gen)50 ‐ 80 mg/kgBW/day , 5 days
Cefixime (cephalosporin 3rd gen)10 ‐ 20 mg/kgBW/day , 10 daysOral
Azithromycin20 mg/kg/day
FluoroquinoloneNot recommended for <14 years old
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RCT comparing Ceftriaxone 75 mg/BW flexible duration to Chloramphenicol 75 mg/BW 14 days give mean defervescence of 5.4 days and 4.2 days respectively. No relaps in Ceftriaxone groups, but 4 cases in Chloramphenicol.
Ceftriaxone 50 mg/BW once a day for 14 days, give mean defervescence of 5.31 days and conciousness improving the first 4 hour in all cases except 2.
Tatli MM, Aktas G, Kosecik M, Yilmaz A. Int J Antimicrobial Agents 2003;21:350-3
Nathin MA, Hadinegoro SR. In RHH Nelwan, editor. Typhoid fever, profile, diagnosisand treatment in the 1990’s. FKUI Press, Jakarta, 1992:133-9
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From 24 isolates, 87% of them sensitive to ampicillin, 96% to chloramphenicol and cotrimoxazole. All isolates were sensitive to Cefixime. Since fluoroquinolone is not recommended for children, cefixime could play a role as a choice in endemic areas with MDRST
In FMUI‐CHD Jakarta, from 25 cases confirmed typhoid fever, cefixime 10‐15 mg/BW give 84% cure rate, with a mean defervescence time of 6.0 ± 3.1 days.
Santillan RM, Garcia GR, Benavente IS, and Garcia. Proc West Pharmacol Soc 2000;43:65-6
Hadinegoro SR, Tumbelaka AR, Satari HI. Sari Pediatri 2001;2(4): 182-7
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Asitromisin
Pada 149 kasus anak dan remaja, yang menderita demamtifoid klinis diberikan asitromisin oral (20 mg/kg/hari) atauseftriakson iv (75 mg/kg/hari) selama 5 hari. Ternyata 30 (94%) kelompok asitromisin serta 35 (97%) darikelompok seftriakson sembuh dan tidak berbeda bermakna. Enam kasus dengan seftriakson mengalami relaps dan tidakada relaps pada kelompok asitromisin. Pengobatan 5 haridengan asitromisin dinyatakan cukup efektif untukmengobati demam tifoid tanpa komplikasi pada anak danremaja.
Frenck RW, Mansour A, Nakhla I, Sultan Y, Putnam S, Wiezerba T et al. Clin Infect Dis. 2004;38(7):951-7.
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Fever defervescence (days)
Ampicilin/Amoxicilin 5,2 ± 3,2 Cotrimoxazole 6,5 ± 1,3 Chloramphenicol 4,2 ± 1,1 Ceftriaxone 5,4 ± 1,5Cefixime 5,7 ± 2,1
Hadinegoro SR. Naskah lengkap PKB Ilmu Kesehatan Anak XLIV. Jakarta: FKUI 2001 :105-16.
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EncephalopatyDexametason 1‐3 mg/ BW/day, 3‐5 daysFluid restriction to 4/5 Acid‐base and electrolyte correction
Peritonitis, intestinal hemorrhageFasting, parenteral nutrition, blood transfusion (ifindicated)parenteral antibiotic
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Hospital Mortality (%)
RSCM 0 ‐ 4,0RSHS 0 ‐ 0,6RSWS 0 ‐ 3,3RSK 0 ‐ 2,0RSMH 0 ‐ 3,2
RSCM Jakarta, RSHS Bandung, RSWS Makasar, RSK Semarang, RSMH Palembang, 1991‐1996
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Typhoid fever in children, mostly > 5 years of ageClinically milder than adult cases, Clinically not specific in younger childrenSensitivity, specificity, and low cost laboratory support neededDrug of choice : chloramphenicolPrevention: vaccine and good hygiene sanitation